Figure 10.

Selected mitocan-based drug combinations retain their synergy in primary AML samples. (A) Synergy landscapes for representative patient sample treated with IACS-010759/vinorelbine, rotenone/2-deoxy-D-glucose, CCCP/dasatinib, or ABT-199/lonidamine. Drug combination landscapes: z-axis, synergy score (ranges from −40, green, to +40, red); x/y-axes, drug1/drug2 concentration range, respectively. For drug1/drug2 concentration ranges refer to Table S5. Drug combination landscapes were built using Bioconductor package “synergyfinder.” One representative replicate (with maximal synergy closest to the average value of three biological replicates) is shown. (B,C) The effect of two selected drug combinations (IACS-010759/vinorelbine or rotenone/2-deoxy-D-glucose) with highest average synergy and corresponding single drugs on primary AML samples or healthy PBMCs. Shown are mean ± SEM from three independent biological replicates. Significance of changes in survival was assessed via Student's t-test. ^***p < 0.001. Black stars indicate comparison of primary AML cells vs. healthy PBMCs under the same treatment condition; purple stars indicate significantly lower survival under combinatorial treatment compared to single mitocan for each cell type; orange stars indicate significantly lower survival under combinatorial treatment compared to single complementary drug for each cell type.